Abstract: S2-17 CRITICAL ROLE OF MAST CELL CHYMASE IN MOUSE ABDOMINAL AORTIC ANEURYSM FORMATION

2009 ◽  
Vol 10 (2) ◽  
pp. e1517
Author(s):  
J Sun ◽  
J Zhang ◽  
J Lindholt ◽  
G Sukhova ◽  
P Libby ◽  
...  
Keyword(s):  
Mast Cell ◽  
Abdominal Aortic Aneurysm ◽  
Aortic Aneurysm ◽  
Critical Role ◽  
Aneurysm Formation ◽  
Abdominal Aortic ◽  
Mast Cell Chymase

scholarly journals Critical Role of Mast Cell Chymase in Mouse Abdominal Aortic Aneurysm Formation

Circulation ◽  
2009 ◽  
Vol 120 (11) ◽  
pp. 973-982 ◽  
Author(s):  
Jiusong Sun ◽  
Jie Zhang ◽  
Jes S. Lindholt ◽  
Galina K. Sukhova ◽  
Jian Liu ◽  
...  
Keyword(s):  
Mast Cell ◽  
Abdominal Aortic Aneurysm ◽  
Aortic Aneurysm ◽  
Critical Role ◽  
Aneurysm Formation ◽  
Abdominal Aortic ◽  
Mast Cell Chymase

scholarly journals Apelin protects against abdominal aortic aneurysm and the therapeutic role of neutral endopeptidase resistant apelin analogs

2019 ◽  
Vol 116 (26) ◽  
pp. 13006-13015 ◽  
Author(s):  
Wang Wang ◽  
Mengcheng Shen ◽  
Conrad Fischer ◽  
Ratnadeep Basu ◽  
Saugata Hazra ◽  
...  
Keyword(s):  
Abdominal Aortic Aneurysm ◽  
Aortic Aneurysm ◽  
Aortic Rupture ◽  
Critical Role ◽  
Neutral Endopeptidase ◽  
Negative Regulator ◽  
Ang Ii ◽  
Direct Role ◽  
Abdominal Aortic

Abdominal aortic aneurysm (AAA) remains the second most frequent vascular disease with high mortality but has no approved medical therapy. We investigated the direct role of apelin (APLN) in AAA and identified a unique approach to enhance APLN action as a therapeutic intervention for this disease. Loss of APLN potentiated angiotensin II (Ang II)-induced AAA formation, aortic rupture, and reduced survival. Formation of AAA was driven by increased smooth muscle cell (SMC) apoptosis and oxidative stress inApln−/yaorta and in APLN-deficient cultured murine and human aortic SMCs. Ang II-induced myogenic response and hypertension were greater inApln−/ymice, however, an equivalent hypertension induced by phenylephrine, an α-adrenergic agonist, did not cause AAA or rupture inApln−/ymice. We further identified Ang converting enzyme 2 (ACE2), the major negative regulator of the renin-Ang system (RAS), as an important target of APLN action in the vasculature. Using a combination of genetic, pharmacological, and modeling approaches, we identified neutral endopeptidase (NEP) that is up-regulated in human AAA tissue as a major enzyme that metabolizes and inactivates APLN-17 peptide. We designed and synthesized a potent APLN-17 analog, APLN-NMeLeu9-A2, that is resistant to NEP cleavage. This stable APLN analog ameliorated Ang II-mediated adverse aortic remodeling and AAA formation in an established model of AAA, high-fat diet (HFD) inLdlr−/−mice. Our findings define a critical role of APLN in AAA formation through induction of ACE2 and protection of vascular SMCs, whereas stable APLN analogs provide an effective therapy for vascular diseases.

The potential role of homocysteine mediated DNA methylation and associated epigenetic changes in abdominal aortic aneurysm formation

2013 ◽  
Vol 228 (2) ◽  
pp. 295-305 ◽  
Author(s):  
Smriti Murali Krishna ◽  
Anthony Dear ◽  
Jeffrey M. Craig ◽  
Paul E. Norman ◽  
Jonathan Golledge
Keyword(s):  
Dna Methylation ◽  
Abdominal Aortic Aneurysm ◽  
Aortic Aneurysm ◽  
Potential Role ◽  
Epigenetic Changes ◽  
Aneurysm Formation ◽  
Abdominal Aortic

scholarly journals The Role of Extracellular Signal-Related Kinase During Abdominal Aortic Aneurysm Formation

2012 ◽  
Vol 215 (5) ◽  
pp. 668-680.e1 ◽  
Author(s):  
Abhijit Ghosh ◽  
Paul D. DiMusto ◽  
Lauren K. Ehrlichman ◽  
Omar Sadiq ◽  
Brendan McEvoy ◽  
...  
Keyword(s):  
Abdominal Aortic Aneurysm ◽  
Aortic Aneurysm ◽  
Aneurysm Formation ◽  
Abdominal Aortic ◽  
Extracellular Signal

scholarly journals Role of Uncoupled Endothelial Nitric Oxide Synthase in Abdominal Aortic Aneurysm Formation

Hypertension ◽  
2012 ◽  
Vol 59 (1) ◽  
pp. 158-166 ◽  
Author(s):  
Ling Gao ◽  
Kin L. Siu ◽  
Karel Chalupsky ◽  
Andrew Nguyen ◽  
Peng Chen ◽  
...  
Keyword(s):  
Nitric Oxide ◽  
Abdominal Aortic Aneurysm ◽  
Nitric Oxide Synthase ◽  
Aortic Aneurysm ◽  
Endothelial Nitric Oxide Synthase ◽  
Aneurysm Formation ◽  
Abdominal Aortic ◽  
Oxide Synthase ◽  
Endothelial Nitric Oxide

scholarly journals Mast Cell Tryptase Deficiency Attenuates Mouse Abdominal Aortic Aneurysm Formation

2011 ◽  
Vol 108 (11) ◽  
pp. 1316-1327 ◽  
Author(s):  
Jie Zhang ◽  
Jiusong Sun ◽  
Jes S. Lindholt ◽  
Galina K. Sukhova ◽  
Mark Sinnamon ◽  
...  
Keyword(s):  
Mast Cell ◽  
Abdominal Aortic Aneurysm ◽  
Aortic Aneurysm ◽  
Mast Cell Tryptase ◽  
Aneurysm Formation ◽  
Abdominal Aortic
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